Fixel Based Analysis Reveals Atypical White Matter Micro- and Macrostructure in Adults With Autism Spectrum Disorder: An Investigation of the Role of Biological Sex.

Melissa Kirkovski,Christian Hyde,Peter H Donaldson,Talitha C Ford,Paul B Fitzgerald,Peter G Enticott,Ian Fuelscher,Susan L Rossell

doi:10.3389/fnint.2020.00040

Melissa Kirkovski, Christian Hyde + Show 6 more

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Atypical white matter (WM) microstructure is commonly implicated in the neuropathophysiology of autism spectrum disorder (ASD). Fixel based analysis (FBA), at the cutting-edge of diffusion-weighted imaging, can account for crossing WM fibers and can provide indices of both WM micro- and macrostructure. We applied FBA to investigate WM structure between 25 (12 males, 13 females) adults with ASD and 24 (12 males, 12 females) matched controls. As the role of biological sex on the neuropathophysiology of ASD is of increasing interest, this was also explored. There were no significant differences in WM micro- or macrostructure between adults with ASD and matched healthy controls. When data were stratified by sex, females with ASD had reduced fiber density and cross-section (FDC), a combined metric comprised of micro- and macrostructural measures, in the corpus callosum, a finding not detected between the male sub-groups. We conclude that micro- and macrostructural WM aberrations are present in ASD, and may be influenced by biological sex.

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Several studies over the last decade have implicated atypical white matter (WM) microstructure in the neurobiology of autism spectrum disorder (ASD; Travers et al, 2012; Aoki et al, 2013; Hoppenbrouwers et al, 2014), a behaviorally characterized, multidimensional neurodevelopmental disorder with varying degrees of symptom severity (American Psychiatric Association, 2013)
In line with previous investigations of biological sex and the neuropathophysiology associated with ASD (Holt et al, 2014; Kirkovski et al, 2015, 2016, 2018; Lei et al, 2019), data were stratified by sex and indices of WM micro- and macrostructure were compared within sex
There was a trend indicative of reduced fiber density (FD) within the corpus callosum (CC), at the posterior midbody/isthmus, in the ASD group compared to age, sex, and IQ matched healthy controls (HC) participants

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Several studies over the last decade have implicated atypical white matter (WM) microstructure in the neurobiology of autism spectrum disorder (ASD; Travers et al, 2012; Aoki et al, 2013; Hoppenbrouwers et al, 2014), a behaviorally characterized, multidimensional neurodevelopmental disorder with varying degrees of symptom severity (American Psychiatric Association, 2013). There are, inconsistencies regarding these findings (see Travers et al, 2012; Aoki et al, 2013; Hoppenbrouwers et al, 2014 for comprehensive reviews and a meta-analysis), and the nature of WM organization in ASD remains unclear. Many diffusion tensor imaging (DTI) approaches are unable to reconcile fiber orientation or the presence of multiple fibers within the one voxel (referred to as crossing fibers). These factors have a substantial impact upon approximations, and the interpretability of findings. Within the ASD literature, CSD has confirmed WM aberration identified using tract-based spatial statistics (TBSS; Roine et al, 2015), and has revealed WM aberration in tracts linking regions of reduced functional connectivity (McGrath et al, 2013)

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